A novel mutation in PRKAR1A gene in a patient with Carney complex presenting with pituitary macroadenoma, acromegaly, Cushing's syndrome and recurrent atrial myxoma

SUMMARY Carney complex (CNC) is a rare syndrome of multiple endocrine and non-endocrine tumors. In this paper we present a 23-year-old Iranian woman with CNC who harbored a novel mutation (c.642dupT) in PRKAR1A gene. This patient presented with pituitary macroadenoma, acromegaly, recurrent atrial myxoma, Cushing's syndrome secondary to primary pigmented nodular adrenocortical disease and pigmented schwanoma of the skin. PRKAR1A gene was PCR amplified using genomic DNA and analyzed for sequence variants which revealed the novel mutation resulting in substitution of amino acid cysteine instead of the naturally occurring valine in the peptide chain and a premature stop codon at position 18 (V215CfsX18). This change leads to development of tumors in different organs due to lack of tumor suppressive activity secondary to failure of synthesis of the related protein.

A novel mutation in PRKAR1A gene in a patient with Carney complex presenting with pituitary macroadenoma, acromegaly, Cushing's syndrome and recurrent atrial myxoma.

Carney complex (CNC) is a rare syndrome of multiple endocrine and non-endocrine tumors. In this paper we present a 23-year-old Iranian woman with CNC who harbored a novel mutation (c.642dupT) in PRKAR1A gene. This patient presented with pituitary macroadenoma, acromegaly, recurrent atrial myxoma, Cushing's syndrome secondary to primary pigmented nodular adrenocortical disease and pigmented schwanoma of the skin. PRKAR1A gene was PCR amplified using genomic DNA and analyzed for sequence variants which revealed the novel mutation resulting in substitution of amino acid cysteine instead of the naturally occurring valine in the peptide chain and a premature stop codon at position 18 (V215CfsX18). This change leads to development of tumors in different organs due to lack of tumor suppressive activity secondary to failure of synthesis of the related protein.

Evaluation of cardiomyopathy diagnosis in heart transplant recipients: comparison of echocardiographic and pathologic classification.

BACKGROUND: Definite diagnosis of cardiomyopathy types can be challenging in end-stage disease process. New growing data have suggested that there is inconsistency between echocardiography and pathology in defining type of cardiomyopathy before and after heart transplantation. The aim of the present study was to compare the pre-heart transplant echocardiographic diagnosis of cardiomyopathy with the results of post-transplant pathologic diagnosis. RESULTS: In this retrospective cross-sectional clinicopathological study, 100 consecutive patients have undergone heart transplantation in Masih-Daneshvari hospital, Tehran, Iran, between 2010 and 2019. The mean age of patients was 40 ± 13 years and 79% of patients were male. The frequency of different types of cardiomyopathy was significantly different between two diagnostic tools (echocardiography versus pathology, P < 0.001). On the other hand, in 24 patients, the results of echocardiography as regard to the type of cardiomyopathy were inconsistent with pathologic findings. CONCLUSION: Based on the findings of the present study, it could be concluded that there is a significant difference between echocardiographic and pathologic diagnosis of cardiomyopathy; therefore, it is necessary to use additional tools for definite diagnosis of cardiomyopathy like advanced cardiac imaging or even endomyocardial biopsy before heart transplantation to reach an appropriate treatment strategy.

Removing an Entrapped Pigtail Catheter by Re-enforcing a Traditional Method.

Right heart catheterization is the main step in the evaluation of pulmonary hypertension including Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and is considered a relatively safe procedure. Complications can occur including perforation, tamponade, bleeding, etc. requiring different types of interventions such as manipulation or surgery. Here, we have described a case of pigtail catheter entrapment and the method we used to free it without invasive measures.

Asymptomatic Giant Lipoma of the Right Ventricular Outflow Tract: A Case Report.

Cardiac lipomas are extremely rare tumors of the heart. They are usually symptomatic and rarely may be found incidentally in autopsies. Here we describe a 23-year-old healthy man, in whose physical examination for employment a murmur was found incidentally. Transthoracic and then transesophageal echocardiographic examination showed a 4-cm oval-shaped mass in the right ventricular outflow tract. He underwent elective surgery, during which the tumor was removed under cardiopulmonary bypass and aortic-cross clamping via right atriotomy. The postoperative course was uneventful, and the patient was in good condition at 1 year's follow-up.

Smoking and wound complications after coronary artery bypass grafting.

BACKGROUND: The harmful effects of smoking on the postsurgical wound healing disturbances have been widely investigated across various surgical procedures. These effects after coronary artery bypass graft (CABG) surgery have been less explored. We aimed to investigate the association of smoking and the wound healing problems in post-CABG patients. MATERIALS AND METHODS: We compared the incidence of wound complications in 405 smokers and 405 nonsmokers who underwent an elective CABG surgery. The incidence of leg and sternal wound complications was evaluated during the first 7 d as well as at a 6-wk postoperative visit. RESULTS: One hundred fifty-six leg wound complications were noted in 132 patients (16.3%). The overall rate of leg wound healing disturbances was significantly higher in smokers than those in nonsmokers (odds ratio, 1.47; 95% confidence interval, 1.109-4.019; P = 0.010). The incidence rates of leg wound edge necrosis and dehiscence were significantly higher in smokers compared with those in nonsmokers (3.7% versus 0.7%, P = 0.004 and 6.6% versus 0.7%, P < 0.0001, respectively). We found no significant differences between the incidence of postoperative leg wound infection, hematoma, wound edema, and seroma in active smokers and those who never smoked. Thirty-seven postsurgical sternal wound complications (4.6%) were developed in 33 patients (4.1%). The overall rate of sternal wound healing disturbances was similar between smokers and nonsmokers. There was a trend between the sternal wound dehiscence and smoking (P = 0.03); however, the other sternal wound complications were not associated with smoking. CONCLUSIONS: Smoking may contribute to the disturbances of wound healing, especially wound dehiscence, in post-CABG patients.

Application of intra-aortic balloon pump in resection and anastomosis of trachea.

The intra-aortic balloon pump (IABP) is a mechanical device used to assist cardiac circulatory function in patients suffering from cardiogenic shock, congestive heart failure, refractory angina and complications of myocardial infarction. While using IABP in cardiac surgery is well established, there are few studies on the utility of IABP support in high-risk cardiac patients undergoing non-cardiac surgery. Major non-cardiac surgeries are associated with high rates of cardiac complications in patients with advanced coronary disease. Recent case studies have reported favorable outcomes with the use of IABP support in non-cardiac surgery in patients with severe cardiac compromise. Using IABP may reduce cardiac complications by providing hemodynamic stability. Here, we present five cases of IABP use in high-risk cardiac patients undergoing resection and anastomosis of the trachea. IABP was inserted prior to induction of anesthesia in four of the cases, while IABP insertion was withheld in one case. In the four cases where IABP support was utilized, the IABP was removed between 6-48 hours postoperatively with no complications. The patient who did not undergo IABP insertion died on the 8th postoperative day due to uncontrollable pulmonary edema and progressive myocardial infarction. We also review the literature and discuss the role of IABP use in non-cardiac surgery.

Effect of pulmonary hypertension on outcome of pulmonary tuberculosis

Background: This study performed at the National Research Institute of Tuberculosis and Lung Disease, Tehran, Iran, aimed to evaluate the effect of concomitant pulmonary hypertension on the outcome of pulmonary tuberculosis. Methods: New cases of pulmonary tuberculosis were recruited for the study. Pulmonary hypertension was defined as systolic pulmonary arterial pressure ≥35 mm Hg estimated by transthoracic Doppler echocardiography. We assessed the relationship between pulmonary hypertension and mortality during the six-month treatment of tuberculosis. Results: Of 777 new cases of pulmonary tuberculosis, 74 (9.5%) had systolic pulmonary arterial pressure ≥35 mm Hg. Ten of them (13.5%) died during treatment compared to 5% of cases with pulmonary arterial pressure less than 35 mm Hg (p = 0.007). Logistic regression analysis showed that pulmonary hypertension and drug abuse remained independently associated with mortality (OR = 3.1; 95% CI: 1.44–6.75 and OR = 4.4; 95% CI: 2.35–8.17, respectively). Conclusion: A significant association was found between mortality and presence of pulmonary hypertension and drug abuse among new cases of pulmonary tuberculosis. .

Late relapse of multiple myeloma presenting as a right atrial mass.

Intracardiac involvement is a rare presentation of relapsed multiple myeloma. We present a case of lobulated mass in the wall of the right atrium, with extension to the inferior vena cava and obliteration and encasement of the interatrial septum in a 57-year-old man, a known case of multiple myeloma, with progressive exertional dyspnea and anasarca.

Successful surgical intervention in an unusual case of Aspergillus endocarditis with acute myeloid leukemia.

Endocarditis due to Aspergillus infection is a rare complication in patients with hematological malignancies. Here, we present a case of aspergillus endocarditis in a patient with acute myeloid leukemia (AML) successfully treated with antifungal therapy and surgical treatment. The patient was a 51 years old male, a known case of AML who was admitted to our medical center for evacuating his valvular vegetations and repairing his atrial septal defect. He underwent an open heart surgery to relinquish his thromboses and also received an antifungal regimen. The patient tolerated the procedure well and eight months after his surgery, the patient remains asymptomatic. Successful treatment of this severe case of aspergillus endocarditis justifies a multidisciplinary method to be as a safe and effective approach to manage these patients.

Cutaneous alternariosis with trichosporon infection in a heart transplant recipient: a case report.

Cutaneous alternariosis infection occurs mainly in immunocompromised individuals. The incidence of alternariosis in a heart transplant recipient is infrequent. Coincidence of the aforementioned infection with additional fugal agents is rare. We describe a case of alternariosis with Trichosporon fungal infection in a patient who was successfully treated with combined antifungal therapy, modulation of immunosuppressive regimen, and blood glucose management. The patient had a good response to treatment, and has had an uneventful 1-year follow-up at the time of this writing.

Comparison of three risk assessment methods for venous thromboembolism prophylaxis.

Venous thromboembolism (VTE) is a major problem for hospitalized patients. Nevertheless, adherence to VTE prophylaxis guidelines is suboptimal, partly because of physicians' neglect due to excessive workload. Simplified risk assessment methods (RAMs) facilitate timely risk stratification and thromboprophylaxis. However, the accuracy of such RAMs has not been extensively studied. Using the prospectively collected data from hospitalized patients of Masih-Daneshvari Hospital, we tested the accuracy of the Goldhaber RAM and the Harinath and St. John RAM for VTE prophylaxis, compared with the eighth edition of the American College of Chest Physicians (ACCP) recommendations. We evaluated 1091 patients. With reference to the ACCP recommendations, both RAMs had high specificities for detection of patients at risk of VTE (97.33 and 99.11%, respectively); however, we found significant interdepartment differences. The Goldhaber RAM had superior accuracy in medical oncology patients (P = 0.03), whereas the Harinath and St. John method was superior among surgical patients (P < 0.001). Overall accuracies of Goldhaber RAM for appropriate VTE risk assessment and for proper detection of at-risk patients were close to 60%. Corresponding figures were close to 70% for the Harinath and St. John method. Simplified VTE prophylaxis RAMs are valuable, especially for transmitting electronic alerts and for timely risk assessment and thromboprophylaxis. Both of the studied RAMs had high specificities and positive-predictive values, minimizing the risk of overprophylaxis. Improving the sensitivity of such RAMs can help for timely risk assessment for a greater array of real-world patients.

Pericardial hydatid cyst in oblique sinus, obstructing all pulmonary veins: a rare presentation.

Hydatid cyst of the heart is an uncommon presentation of hydatidosis. We present a case of pericardial hydatid cyst in pericardial oblique sinus with extension to posterior wall of left atrium (LA), occluding all pulmonary vein ostia in a 35 year-old female with progressive dyspnea and severe orthopnea.

Uremic pleuritis in chronic hemodialysis patients.

Chronic hemodialysis (HD) patients are predisposed to several complications associated with pleural effusion. In addition, uremia can directly cause pleuritis. However, there are inadequate data about pathogenesis and natural course of uremic pleuritis. In this study, 76 chronic HD patients with pleural effusion admitted to the Respiratory Center of Masih Daneshvari Hospital, in Tehran, Iran between June 2005 and May 2011 were evaluated to figure out the etiology of their pleural disease. Among these patients, patients with uremic pleuritis were identified and studied. The rate of uremic pleuritis was 23.7%. Other frequent etiologies of pleural effusion were parapneumonic effusion (23.7%), cardiac failure (19.7%), tuberculosis (6.6%), volume overload, malignancy, and unknown. In patients with uremic pleuritis, dyspnea was the most common symptom, followed by cough, weight loss, anorexia, chest pain, and fever. Compared to patients with parapneumonic effusion, patients with uremic effusion had a significantly higher rate of dyspnea and lower rate of cough and fever. Pleural fluid analysis showed that these patients had a significantly lower pleural to serum lactic dehydrogenase ratio, total pleural leukocytes, and polymorphonuclear count compared to patients with parapneumonic effusion. Improvement was achieved in 94.1% of patients with uremic pleuritis by continuation of HD, chest tube insertion or pleural decortication; an outcome better than the previous reports. Despite the association with an exudative effusion, inflammatory pleural reactions in patients with uremic pleuritis may not be as severe as infection-induced effusions. Owing to the advancement in HD technology and other interventions, outcome of uremic pleuritis may be improved.

Risk factors affecting the survival rate in patients with symptomatic pericardial effusion undergoing surgical intervention.

OBJECTIVES: The optimal management and treatment of pericardial effusion are still controversial. There is limited data related to the risk factors affecting survival in these patients. The aim of this study was to determine the risk factors affecting the survival rate of patients with symptomatic pericardial effusion who underwent surgical interventions. METHODS: From 2004 to 2011, we retrospectively analysed 153 patients who underwent subxiphoid pericardial window as their surgical intervention to drain pericardial effusions at the National Research Institute of Tuberculosis and Lung diseases (NRITLD). To determine the effects of risk factors on survival rate, demographic data, clinical records, echocardiographic data, computed tomographic and cytopathological findings and also operative information of patients were recorded. Patients were followed annually until the last clinical follow-up (August 2011). To determine the prognostic factors affecting survival, both univariate analysis and multivariate Cox proportional hazards model were utilized. RESULTS: There were 89 men and 64 women with a mean age of 50.3 ± 15.5 years. The most prevalent symptom was dyspnoea. Concurrent malignancies were present in 66 patients. Lungs were the most prevalent primary site for malignancy. The median duration of follow-up was 15 (range 1-85 months). Six-month, 1-year and 18-month survival rates were 85.6, 61.4 and 36.6%, respectively. In a multivariate analysis, positive history of lung cancer (hazard ratio [HR] 2.894, 95% confidence interval [CI] 1.362-6.147, P = 0.006) or other organ cancers (HR 2.315, 95% CI 1.009-50311, P = 0.048), presence of a mass in the computed tomography (HR 1.985, 95% CI 1.100-3.581, P = 0.023), and echocardiographic findings compatible with tamponade (HR 1.745, 95% CI 1.048-2.90 P = 0.032) were the three independent predictors of postoperative death. CONCLUSIONS: In the surgical management of pericardial effusion, patients with underlying malignant disease, especially with lung cancer, patients with a detectable invasion of thorax in computed tomography and those with positive echocardiographic findings compatible with tamponade have a poor survival. Therefore, minimally invasive therapies could be considered as a more acceptable alternative for these high-risk patients.

Chest physicians' knowledge of appropriate thromboprophylaxis: insights from the PROMOTE study.

Venous thromboembolism (VTE) is a major cause of in-hospital mortality. Several international guidelines provide thromboprophylaxis recommendations; however, guidelines adherence is missing worldwide. We evaluated the chest physicians' knowledge regarding VTE prophylaxis, using a systematically developed questionnaire. The Prophylaxis-foR-venOus-throMbOembolism-assessmenT-questionnairE (PROMOTE) questionnaire was developed using an algorithm encompassing the most important VTE prophylaxis topics and included 13 clinical scenarios. Responses were evaluated with reference to the eighth edition of American College of Chest Physicians guidelines for VTE prevention to assess thromboprophylaxis appropriateness. The questionnaires were distributed during the fourth International Congress on Pulmonary Disease, Intensive Care and Tuberculosis. From the 88 received questionnaires (response rate: 39.8%), 82 were acceptable (62 men, 20 women). The most commonly cited VTE risk factors were immobility (79.2%), surgery (68.2%), and cancer (60.9%). The mean correct response ratio to the questions was 67% [95% confidence interval (CI) 64-70%] with highest appropriateness ratios amongst cardiologists (77.1 ±â€Š5.8%) and lowest ratios among thoracic surgeons (59.2 ±â€Š5%). Physicians' specialty had a significant effect on the overall appropriateness (P = 0.04) and most of appropriateness subcategories. Thoracic surgeons had the lowest rate of over-prophylaxis (P = 0.02). Years passed from graduation were inversely associated with overall appropriateness (P = 0.006). Physicians with academic engagements had a higher overall appropriateness (P = 0.04). We found a wide gap between the guideline recommendations and the responses. PROMOTE is the first systematically developed questionnaire that addresses chest physicians' thromboprophylaxis knowledge and could be useful to strategies to improve VTE prophylaxis. Because of the dissimilar prophylaxis pitfalls of different specialists, distinct educational programs seem necessary to improve their knowledge of proper VTE prophylaxis.

Dexter versus sinister deep vein thrombosis: which is the more sinister? Findings from the NRITLD DVT registry.

Deep vein thrombosis (DVT) is a major health problem. Despite the wealth of studies on its epidemiology, few have described the thrombus sidedness and particularly the association of thrombus sidedness with clinical presentation and subsequent complications. This article reviews current knowledge regarding this topic and in light of recent data from a large prospective study. This is the first report from the prospective National Research Institute of Tuberculosis and Lung Disease DVT registry. Patients with ultrasound-confirmed symptomatic DVT were enrolled, and thrombus sidedness was investigated in each case. Computed tomography pulmonary angiography was used to diagnose coexisting pulmonary embolism (PE) in DVT patients with suggestive symptoms. Embolic burden score was calculated for those with PE. From the total of 100 patients, 45 had left-sided DVT, 41 had right-sided DVT, and 14 had bilateral DVT. Presenting symptoms and comorbidities were comparable, except for cancer, which was more common in those with right-sided involvement (either right-sided or bilateral DVT; P = 0.004). Compared with those with left-sided DVT, PE happened more frequently in right-sided DVT patients. Right-sided DVT patients also had a higher rate of massive PE ( P = 0.03) and a greater mean embolic burden (13.32 ± 1.63 versus 6.05 ± 1.06; P = 0.001). These findings support raised awareness for global reconsideration of the assumption of complete identicalness of right-sided and left-sided DVT. Although future studies are needed to better elucidate epidemiological and prognostic differences based on the thrombus sidedness, our preliminary findings suggest that the two are not completely identical and right-sided DVT might be more ominous.

Correlation between the Pulmonary Artery Pressure Measured in Echocardiography and Pulmonary Artery Diameter in the CT-Scan of Patients Suffering from Interstitial Lung Disease.

BACKGROUND: Pulmonary hypertension (PH) is a significant cause of morbidity and mortality in patients suffering from pulmonary parenchymal diseases. Diagnosis of PH has always been a major clinical dilemma due to its non-specific clinical manifestations. However, diagnosing PH and determining its severity are essential for the prognosis and treatment planning in PH patients. This study aimed at evaluating the correlation between the pulmonary artery diameter (PAD) in the CT-scan and pulmonary artery pressure (PAP) in echocardiography of patients. MATERIALS AND METHODS: PAD was evaluated in the CT-scan of 117 patients suffering from interstitial lung disease (ILD) and the correlation between PAD and PAP was studied. A receiver operating characteristic curve (ROC curve) which is indicative of the precision of the diagnostic test was drawn to find the cut off point for the MPAD representing PH. The area under the curve was also calculated in order to define the discriminative power of the test. RESULTS: PAP higher than 25 mmHg was considered as PH. PAD over 29 mm reported in the CT-scan for the diagnosis of PH in ILD patients had sensitivity of 63% and specificity of 41.5%. No significant linear correlation was found between PAD and PAP (P-value = 0.17, r = 0.15). The area under the ROC curve was calculated to be 0.49 in the cutoff point of 29 mm for determining PH (CI 95% = 0.38-0.60, P = 0.89). CONCLUSION: ROC curve showed a weak discriminative power. PAD had low sensitivity and specificity in the CT-scan for the diagnosis of PH. Therefore, we conclude that CT-scan alone is not helpful in finding PH cases and further examinations are required.

Noninvasive assessment of acute cardiopulmonary effects of an oral single dose of sildenafil in patients with idiopathic pulmonary hypertension.

We aimed to assess the acute cardiopulmonary effects of a 100-mg oral single dose of sildenafil in patients with idiopathic pulmonary hypertension (IPAH) using a well-validated but less-used noninvasive echocardiographic method for the measurement of both systolic and diastolic pulmonary artery pressure (PAP), by tricuspid regurgitation (TR) velocity curve analysis. We studied 12 consecutive patients with IPAH (10 patients with New York Heart Association functional class III, and 2 patients with functional class II). A 100-mg oral single dose of sildenafil was added to previous medications of all patients and its immediate effects were evaluated 1, 5, and 12 h after treatment. Using paired analysis, administration of a 100-mg oral single dose of sildenafil led to a significant reduction in mean PAP and a remarkable increase in pulmonary acceleration time (PAT) 1 h after treatment (P = 0.000; 95% confidence interval [CI] 18.99-26.00 and P = 0.005; 95% CI -12.89 to -2.95, respectively). In addition, although the right heart dimensions (right atrium and right ventricle) showed a trend toward improvement, the differences were not statistically significant (P = 0.13 and P = 0.08, respectively). Our results demonstrated that Doppler examination of TR alone can be easily used for the estimate of systolic and diastolic PAP in patients with IPAH. This study also shows that sildenafil is the only drug given orally that can evaluate the vasodilatory capacity of the pulmonary vascular bed in patients with IPAH, with promising effects on mPAP and PAT in these patients.

Incidence of fever and bacteriemia following flexible fiberoptic bronchoscopy: a prospective study.

The latest American Heart Association (AHA) statement for preventing infectious endocarditis, has not recommended prophylactic antibiotic therapy prior to fiberoptic bronchoscopy (FB) except for patients with preexisting predisposing cardiac conditions. Our aim was to determine the incidence of bacteriemia and fever following FB in our experience and compare with those which have been mentioned in AHA guideline as well as other studies. Venous blood of 85 consecutive patients was evaluated for both aerobic and anaerobic cultures before (for detecting possible previous bacteriemia) and after FB. None of the patients were treated with antibiotics prior to the procedure. All the patients were examined during the first 24 hours after FB for detecting fever defined as temperature more than 38 °C. Positive hemocultures were noted in 7 (8.2 %) patients after FB examination. Coagulase negative Staphylococcus, coagulase positive Staphylococcus, beta haemolytic Streptococcus, Citrobacter freundii and Streptococcus viridans were found in 4, 1, 1 and 1 cultures of patients, respectively. By excluding 6 contaminated samples, the rate of bacteriemia reduced to 1 (1.1%) patient in whom the identical pathogen (Streptococcus viridans) was found both in bronchial lavage and venous blood culture. We also found fever in 9 (10.5 %) cases in the first 24 hours following the bronchoscopy. Our results were in consistent with AHA recommendations regarding prevention of infectious endocarditis as a practical gridline in patients who schedule for FB. Besides, transient fever following bronchoscopy is a common self-limited event which does not need medical intervention.